Experimentelle Kinderonkologie

Der Fokus unserer Arbeiten liegt auf der Erforschung der Pathogenese des Neuroblastoms und der Übertragung neuer molekularer Erkenntnisse in die klinische Anwendung. Unser Ziel ist, durch ein besseres Verständnis der Tumorbiologie die Behandlungsmöglichkeiten von Neuroblastom-Patienten zu verbessern.

In Deutschland erkranken jährlich etwa 130 Kinder an einem Neuroblastom. Das Neuroblastom ist ein Tumor, der sich zumeist im Bauch- oder Brustraum aus Zellen des peripheren Nervensystems entwickelt. Die Erkrankung weist äußerst unterschiedliche Verläufe auf: Bei etwa der Hälfte der betroffenen Kinder kommt es zu einem aggressiven Tumorwachstum, das trotz intensiver Behandlung oft zum Tod der Patienten führt. In anderen Fällen hingegen bildet sich das Neuroblastom spontan zurück und die Erkrankung heilt ohne eine belastende Chemotherapie aus. Die genetischen Ursachen und die molekularen Prozesse dieser unterschiedlichen Verlaufsformen sind bis heute nicht komplett verstanden.

Zur umfassenden molekularen Charakterisierung der verschiedenen Verlaufsformen des Neuroblastoms nutzen wir moderne Hochdurchsatz-Technologien, wie z.B. Next Generation Sequencing und Microarray-Profiling. Hierdurch können wir tumorspezifische genetische Veränderungen identifizieren, die Aufschluss über die molekularen Mechanismen von Tumor-Regression und –Progression geben und den klinischen Verlauf der Patienten vorhersagen können. Die funktionelle Relevanz der genetischen Veränderungen prüfen wir in Zellkultur-Experimenten und transgenen Mausmodellen. Ein besonderer Fokus liegt auf der Entwicklung neuer Therapieansätze, die gezielt in krebsspezifische Signalwege des Tumors eingreifen. Die Ergebnisse unserer experimentellen Studien nutzen wir zur Entwicklung klinischer Studien, in denen neue diagnostische und therapeutische Verfahren unter kontrollierten Bedingungen geprüft werden.

Das Team

Dr. rer nat. Justus Ackermann
Dr. rer. medic. Christoph Bartenhagen
Dr. Janina Fischer
Dr. Carolina Sterz
Yvonne Kahlert
Anne Engesser
Andrea Krämer, M.Sc.
Elisabeth Arnz, cand. med.
Christine Stindt, cand. med.
Frederik Sand, cand. med.
Esther Walter, cand. med.

Veröffentlichungen

Publikationsliste Prof. Dr. Matthias Fischer

I Originalarbeiten

Hamisch C, Kickingereder P, Fischer M, Simon T, Ruge MI
Update on the diagnostic value and safety of stereotactic biopsy for pediatric brainstem tumors: a systematic review and meta-analysis of 735 cases. Journal of Neurosurgery: Pediatrics, in press.

Thole T, Lodrini M, Fabian J, Wünschel J, Pfeil S, Hielscher T, Kopp-Schneider A, Heinicke U, Fulda S, Witt O, Eggert A, Fischer M, Deubzer H
Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival. Cell Death Dis, 2017, 8(3): e2635.

Geoerger B, Bourdeaut F, DuBois SG, Fischer M, Geller JI, Gottardo NG, Marabelle A, Pearson ADJ, Modak S, Cash T, Robinson GW, Motta M, Matano A, Bhansali SG, Dobson JR, Parasuraman S, Chi SN
A phase I study of the CDK4/6 inhibitor Ribociclib (LEE011) in pediatric patients with malignant rhabdoid tumors, neuroblastoma, and other solid tumors. Clin Cancer Res, Epub ahead of print.

Pajtler KW, Sadowski N, Ackermann S, Althoff K, Schönbeck K, Batzke K, Schäfers S, Odersky A, Heukamp L, Astrahantseff K, Künkele A, Deubzer HE, Schramm A, Sprüssel A, Thor T, Lindner S, Eggert A, Fischer M, Schulte JH
The GSK461364 PLK1 inhibitor exhibits strong antitumoral activity in preclinical neuroblastoma models. Oncotarget, 2017, 8(4): 6730-6741.

Fabian J, Opitz D, Althoff K, Lodrini M, Hero B, Volland R, Beckers A, De Preter K, Decock A, Patil N, Abba M, Kopp-Schneider A, Astrahantseff K, Wünschel J, Pfeil S, Ercu M, Künkele A, Hu J, Thole T, Schweizer L, Mechtersheimer G, Carter D, Cheung BB, Popanda O, von Deimling A, Koster J, Versteeg R, Schwab M, Marshall GM, Speleman F, Erb U, Zoeller M, Allgayer H, Simon T, Fischer M, Kulozik AE, Eggert A, Witt O, Schulte JH, Deubzer H
MYCN and HDAC5 transcriptionally repress CD9 to trigger invasion and metastasis in neuroblastoma. Oncotarget, 2016, 7(41): 66344-66359.

Dorneburg C, Goß AV, Fischer M, Roels F, Barth TF, Berthold F, Kappler R, Oswald F, Siveke JT, Molenaar JJ, Debatin KM, Beltinger C
g-secretase inhibitor I inhibits neuroblastoma cells, with NOTCH and the proteasome among its targets. Oncotarget, 2016, 7(39): 62799-62813.

Duffy DJ, Krstic A, Schwarzl T, Halasz M, Iljin K, Fey D, Haley B, Whilde J, Haapa-Paananen S, Fey V, Fischer M, Westermann F, Henrich KO, Bannert S, Higgins DG, Kolch W
Wnt signalling is a bi-directional vulnerability of cancer cells. Oncotarget, 2016, 7(37): 60310-60331.

Henrich KO, Bender S, Saadati M, Dreidax D, Gartlgruber M, Shao C, Herrmann C, Wiesenfarth M, Parzonka M, Wehrmann L, Fischer M, Duffy DJ, Bell E, Torkov A, Schmezer P, Plass C, Höfer T, Benner A, Pfister SM, Westermann F
Integrative Genome-Scale Analysis Identifies Epigenetic Mechanisms of Transcriptional Deregulation in Unfavorable Neuroblastomas. Cancer Res, 2016, 76(18): 5523-5537.

Ribeiro D, Klarqvist MDR, Westermark UK, Oliynyk G, Dzieran J, Kock A, Savatier Banares C, Hertwig F, Johnsen JI, Fischer M, Kogner P, Lovén J, Arsenian Henriksson M
Regulation of the nuclear hormone receptor family by MYCN-driven miRNAs impacts neural differentiation and survival in neuroblastoma patients. Cell Rep, 2016, 16(4): 979-993.

Worst BC, van Tilburg CM, Balasubramanian GP, Fiesel P, Witt R, Freitag A, Boudalil M, Previti C, Wolf S, Schmidt S, Chotewutmontri S, Bewerunge-Hudler M, Schick M, Schlesner M, Hutter B, Taylor L, Borst T, Sutter C, Bartram CR, Milde T, Pfaff E, Kulozik AE, von Stackelberg A, Meisel R, Borkhardt A, Reinhardt D, Klusmann JH, Fleischhack G, Tippelt S, Dirksen U, Jürgens H, Kramm CM, von Bueren AO, Westermann F, Fischer M, Burkhardt B, Wößmann W, Nathrath M, Bielack SS, Frühwald MC, Fulda S, Klingebiel T, Koscielniak E, Schwab M, Tremmel R, Hernáiz Driever P, Schulte JH, Brors B, von Deimling A, Lichter P, Eggert A, Capper D, Pfister SM, Witt O
Next-generation personalized medicine for high-risk pediatric cancer patients - the INFORM pilot study. Eur J Cancer, 2016, 65: 91-101.

Damm-Welk C, Siddiqi F, Fischer M, Hero B, Narayanan V, Camidge DR, Harris M, Burke A, Lehrnbecher T, Pulford K, Oschlies I, Siebert R, Turner S, Woessmann W
Differential Anti-ALK Immune Response In Patients With Varying ALK-Positive Malignancies As Measured By Anti-ALK Antibody Titres. J Cancer, 2016, 7(11): 1383-1387.

Formicola D, Petrosino G, Lasorsa VA, Pignataro P, Cimmino F, Vetrella S, Longo L, Tonini GP, Oberthuer A, Iolascon A, Fischer M, Capasso M
An 18 gene expression-based score classifier predicts the clinical outcome in stage 4 neuroblastoma. J Transl Med, 2016, 14(1): 142.

Ikram F, Ackermann S, Kahlert Y, Volland R, Roels F, Engesser A, Hertwig F, Kocak H, Hero B, Dreidax D, Henrich KO, Berthold F, Nürnberg P, Westermann F, Fischer M
Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma. Mol Oncol, 2016, 10(2): 344-359.

Riehl LM, Schulte JH, Mulaw MA, Dahlhaus M, Fischer M, Schramm A, Eggert A, Debatin KM, Beltinger C
The mitochondrial genetic landscape in neuroblastoma from tumor initiation to relapse. Oncotarget, 2016, 7(6): 6620-6625.

Thompson D, Vo KT, London WB, Fischer M, Ambros PF, Nakagawara A, Brodeur GM, Matthay KK, DuBois SG
Identification of patient subgroups with markedly disparate rates of MYCN amplification in neuroblastoma:  A report from the International Neuroblastoma Risk Group (INRG) project. Cancer, 2016, 122(6): 935-945.

Dahlhaus M, Burkovski A, Hertwig F, Mussel C, Volland R, Fischer M, Debatin KM, Kestler HA, Beltinger C
Boolean modeling identifies greatwall/MASTL as an important regulator in the AURKA network of neuroblastoma. Cancer Lett, 2016, 371(1): 79-89.

Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, Krämer A, Roncaioli JL, Sand F, Heuckmann J, Ikram F, Schmidt R, Ackermann S, Engesser A, Kahlert Y, Vogel W, Altmüller J, Nürnberg P, Thierry-Mieg J, Thierry-Mieg D, Mariappan A, Heynck S, Mariotti E, Henrich KO, Glöckner C, Bosco G, Leuschner I, Schweiger MR, Savelyeva L, Watkins SC, Shao C, Bell E, Höfer T, Achter V, Lang U, Theissen J, Volland R, Saadati M, Eggert A, de Wilde B, Berthold F, Peng Z, Zhao C, Shi L, Ortmann M, Büttner R, Perner S, Hero B, Schramm A, Schulte JH, Herrmann C, O’Sullivan RJ, Westermann F, Thomas RK, Fischer M
Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature, 2015, 526: 700-704.

Fey D, Halasz M, Dreidax D, Kennedy SP, Hastings JF, Rauch N, Garcia Munoz A, Pilkington R, Fischer M, Westermann F, Kolch W, Kholodenko BN, Croucher DR
Patient-specific simulations of JNK pathway activity correlate apoptotic signaling with neuroblastoma patient survival. Sci Signal, 2015, 8(408): ra130.

Duffy DJ, Krstic A, Halasz M, Schwarzl T, Fey D, Iljin K, Mehta JP, Killick K, Whilde J, Turriziani B, Haapa-Paananen S, Fey V, Fischer M, Westermann F, Henrich KO, Bannert S, Higgins DG, Kolch W
Integrative omics reveals MYCN as a global suppressor of cellular signalling and enables network-based therapeutic target discovery in neuroblastoma. Oncotarget, 2015, 6(41): 43182-201.

Carter DR, Murray J, Cheung BB, Gamble L, Koach J, Tsang J, Sutton S, Kalla H, Syed S, Gifford AJ, Issaeva N, Biktasova A, Atmadibrata B, Sun Y, Sokolowski N, Ling D, Kim PY, Webber H, Clark A, Ruhle M, Liu B, Oberthuer A, Fischer M, Byrne J, Saletta F, Thwe LM, Purmal A, Haderski G, Burkhart C, Speleman F, De Preter K, Beckers A, Ziegler D, Liu T, Gurova KV, Gudkov AV, Norris MD, Haber M, Marshall GM
Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma. Sci Transl Med, 2015, 7(312): 312ra176.

Abdallah AT, Fischer M, Nürnberg P, Nothnagel M, Frommolt P
CoNCoS: Copy number estimation in cancer with controlled support. J Bioinf Comput Biol, 2015, 13(5): 1550027.

Schramm A, Köster J, Assenov Y, Althoff K, Peifer M, Mahlow E, Odersky A, Beisser D, Ernst C, Henssen AG, Stephan H, Schröder C, Heukamp L, Engesser A, Kahlert Y, Theissen J, Hero B, Roels F, Altmüller J, Nürnberg P, Astrahantseff K, Gloeckner C, De Preter K, Plass C, Lee S, Lode HN, Henrich KO, Gartlgruber M, Speleman F, Schmezer P, Westermann F, Rahmann S*, Fischer M*, Eggert A*, Schulte JH*
Mutational dynamics between primary and relapse neuroblastomas. Nat Genet, 2015, 47(8): 872-877; *equal contribution.
       
Zhang W, Yu Y, Hertwig F, Thierry-Mieg J, Zhang W, Thierry-Mieg D, Wang J, Furlanello C, Devanarayan V, Cheng J, Deng Y, Hero B, Hong H, Jia M, Li L, Lin SM, Nikolsky Y, Oberthuer A, Qing T, Su Z, Volland R, Wang C, Wang MD, Ai J, Albanese D, Asgharzadeh S, Avigad S, Bao W, Bessarabova M, Brilliant MH, Brors B, Chierici M, Chu TM, Zhang J, Grundy RG, He MM, Hebbring S, Kaufman HL, Lababidi S, Lancashire LJ, Li Y, Lu XX, Luo H, Ma X, Ning B, Noguera R, Peifer M, Phan JH, Roels F, Rosswog C, Shao S, Shen J, Theissen J, Tonini GP, Vandesompele J, Wu PY, Xiao W, Xu J, Xu W, Xuan J, Yang Y, Ye Z, Dong Z, Zhang KK, Yin Y, Zhao C, Zheng Y, Wolfinger RD, Shi T, Malkas LH, Berthold F, Wang J, Tong W, Shi L, Peng Z, Fischer M
Comparison of RNA-seq and microarray-based models for clinical endpoint prediction. Genome Biol, 2015, 16(1): 133.

Lindner S, Bachmann HS, Odersky A, Schaefers S, Klein-Hitpass L, Hero B, Fischer M, Eggert A, Schramm A, Schulte JH
Absence of telomerase reverse transcriptase promoter mutations in neuroblastoma. Biomed Rep, 2015, 3(4): 443-446.

Lau DT, Flemming CL, Gherardi S, Perini G, Oberthuer A, Fischer M, Juraeva D, Brors B, Xue C, Norris MD, Marshall GM, Haber M, Fletcher JI, Ashton LJ
MYCN amplification confers enhanced folate dependence and methotrexate sensitivity in neuroblastoma. Oncotarget, 2015, 6(17): 15510-15523.

Oberthuer A, Juraeva D, Hero B, Volland R, Sterz C, Schmidt R, Faldum A, Kahlert Y, Engesser A, Asgharzadeh S, Seeger R, Ohira M, Nakagawara M, Scaruffi P, Tonini GP, Janoueix-Lerosey I, Delattre O, Schleiermacher G, Vandesompele J, Speleman F, Noguera R, Piqueras M, Bénard J, Valent A, Avigad S, Yaniv I, Grundy RG, Ortmann M, Shao C, Schwab M, Eils R, Simon T, Theissen J, Berthold F, Westermann F, Brors B, Fischer M
Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular prognostic markers. Clin Cancer Res, 2015, 21(8): 1904-1915.

Ackermann S, Kocak H, Hero B, Ehemann V, Kahlert Y, Oberthür A, Roels F, Theißen J, Odenthal M, Berthold F, Fischer M
FOXP1 inhibits cell growth and reduces tumorigenicity of neuroblastoma. BMC Cancer, 2014, 14(1): 840.

Su Z, Fang H, Hong H, Shi L, Zhang W, Zhang W, Zhang Y, Dong Z, Lancashire LJ, Bessarabova M, Yang X, Ning B, Gong B, Meehan J, Xu J, Ge W, Perkins R, Fischer M*, Tong W*
An investigation of biomarkers derived from legacy microarray data for their utility in the RNA-seq era. Genome Biol, 2014, 15(12): 523; *Corresponding author.

Pandey GK, Mitra S, Subhash S, Hertwig F, Kanduri M, Mishra K, Fransson S, Ganeshram A, Mondal T, Bandaru S, Östensson M, Akyürek LM, Abrahamsson J, Pfeifer S, Larsson E, Shi L, Peng Z, Fischer M, Martinsson T, Hedborg F, Kogner P, Kanduri C
Neuroblastoma transcriptome sequencing reveals a risk associated long noncoding RNA NBAT-1 that controls tumor progression via regulating cell proliferation and neuronal differentiation. Cancer Cell, 2014, 26(5): 722-737.

Dreidax D, Bannert S, Henrich KO, Schröder C, Bender S, Oakes CC, Lindner S, Schulte J, Duffy D, Schwarzl T, Saadati M, Ehemann V, Benner A, Pfister S, Fischer M, Westermann F
p19-INK4d inhibits neuroblastoma cell growth, induces differentiation and is hypermethylated and downregulated in MYCN-amplified neuroblastomas. Hum Mol Genet, 2014, 23(25): 6826-6837.

Su Z, Łabaj PP, Li S, Thierry-Mieg J, Thierry-Mieg D, Shi W, Wang C, Schroth GP, Setterquist RA, Thompson JF, Jones WD, Xiao W, Xu W, Jensen RV, Kelly R, Xu J, Conesa A, Furlanello C, Gao H, Hong H, Jafari N, Letovsky S, Liao Y, Lu F, Oakeley EJ, Peng Z, Praul CA, Santoyo-Lopez J, Scherer A, Shi T, Smyth GK, Staedtler F, Sykacek P, Tan XX, Thompson EA, Vandesompele J, Wang MD, Wang J, Wolfinger RD, Zavadil J, Auerbach SS, Bao W, Binder H, Blomquist T, Brilliant MH, Bushel PR, Cai W, Catalano JG, Chang CW, Chen T, Chen G, Chen R, Chierici M, Chu TM, Clevert DA, Deng Y, Derti A, Devanarayan V, Dong Z, Dopazo J, Du T, Fang H, Fang Y, Fasold M, Fernandez A, Fischer M, Furió-Tari P, Fuscoe JC, Gaj S, Gandara J, Gao H, Ge W, Gondo Y, Gong B, Gong M, Gong Z, Green B, Guo C, Guo L, Guo LW, Hadfield J, Hellemans J, Hochreiter S, Jia M, Jian M, Johnson CD, Kay S, Kleinjans J, Lababidi S, Levy S, Li QZ, Li L, Li L, Li P, Li Y, Li H, Li J, Li S, Lin SM, López FJ, Lu X, Luo H, Ma X, Meehan J, Megherbi DB, Mei N, Mu B, Ning B, Pandey A, Pérez-Florido J, Perkins RG, Peters R, Phan JH, Pirooznia M, Qian F, Qing T, Rainbow L, Rocca-Serra P, Sambourg L, Sansone SA, Schwartz S, Shah R, Shen J, Smith TM, Stegle O, Stralis-Pavese N, Stupka E, Suzuki Y, Szkotnicki LT, Tinning M, Tu B, van Delft J, Vela A, Venturini E, Walker SJ, Wan L, Wang W, Wang J, Wang J, Wieben ED, Willey JC, Wu PY, Xuan J, Yang Y, Ye Z, Yin Y, Yu Y, Yuan YC, Zhang J, Zhang KK, Zhang W, Zhang W, Zhang Y, Zhao C, Zheng Y, Zhou Y, Zumbo P, Tong W, Kreil DP, Mason CE, Shi L
A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequence Quality Control consortium. Nat Biotechnol, 2014, 32(9): 903-914.

Walz S, Lorenzin F, Morton J, Wiese KE, von Eyss B, Herold S, Rycak L, Dumay-Odelot H, Karim S, Bartkuhn M, Roels F, Wuestefeld T, Fischer M, Teichmann M, Zender L, Wei CL, Sansom O, Wolf E, Eilers M
Activation and repression by oncogenic Myc shape tumour-specific gene expression profiles. Nature, 2014, 511(7510): 483-487.

Theissen J, Oberthuer A, Hombach A, Volland R, Hertwig F, Fischer M, Spitz R, Zapatka M, Brors B, Ortmann M, Simon T, Hero B, Berthold F
Chromosome 17/17q gain and unaltered profiles in high resolution array-CGH are prognostically informative in neuroblastoma. Gene Chromosome Canc, 2014, 53(8): 639-649.

Fabian J, Lodrini M, Oehme I, Schier M, Thole T, Hielscher T, Kopp-Schneider A, Opitz L, Capper D, von Deimling A, Wiegand I, Milde T, Mahlknecht U, Westermann F, Popanda O, Roels F, Hero B, Berthold F, Fischer M, Kulozik A, Witt O, Deubzer H
GRHL1 acts as tumor suppressor in neuroblastoma and is negatively regulated by MYCN and
HDAC3. Cancer Res, 2014, 74(9): 2604-2616.

Schelhorn SE, Fischer M, Tolosi L, Altmüller J, Nürnberg P, Pfister H, Lengauer T, Berthold F
Sensitive detection of viral transcripts in human tumor transcriptomes. PLoS Comput Biol, 2013, 9(10): e1003228.

Brockmann M, Poon E, Berry T, Carstensen A, Deubzer HE, Rycak L, Jamin Y, Thway K, Robinson SP, Roels F, Witt O, Fischer M, Chesler L, Eilers M
Small molecule inhibitors of Aurora-A induce proteasomal degradation of N-Myc in childhood neuroblastoma. Cancer Cell, 2013, 24(1): 75-89.

Lodrini M, Oehme I, Schroeder C, Milde T, Schier M, Kopp-Schneider A, Schulte J,  Fischer M, De Preter K, Pattyn F, Castoldi M, Muckenthaler M, Kulozik A, Westermann F, Witt O, Deubzer H
MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma. Nucleic Acids Res, 2013, 41(12): 6018-6033.

Aschoff M, Hotz-Wagenblatt A, Glatting KH, Fischer M, Eils R, König R
SplicingCompass: differential splicing detection using RNA-Seq data. Bioinformatics, 2013, 29(9): 1141-1148.

Kocak H, Ackermann S, Hero B, Kahlert Y, Oberthuer A, Juraeva D, Roels F, Theissen J, Westermann F, Deubzer H, Ehemann V, Brors B, Odenthal M, Berthold F, Fischer M
Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma. Cell Death Dis, 2013, 4:e586.

Dreidax D, Gogolin S, Schroeder C, Muth D, Brueckner LM, Hess EM, Zapatka M, Theißen J, Fischer M, Ehemann V, Schwab M, Savelyeva L, Westermann F
Low p14ARF expression in neuroblastoma cells is associated with repressed histone mark status, and enforced expression induces growth arrest and apoptosis. Hum Mol Genet, 2013, 22(9): 1735-1745.

Molenaar J, Domingo-Fernández R, Ebus M, Lindner S, Koster J, Drabek K, Mestdagh P, van Sluis P, Valentijn L, van Nes J, Broekmans M, Haneveld F, Volckmann R, Bray I, Heukamp L, Sprüssel A, Thor T, Kieckbusch K, Klein-Hitpass L, Fischer M, Vandesompele J, Schramm A, van Noesel M, Varesio L, Speleman F, Eggert A, Stallings R, Caron H, Versteeg R, Schulte JH
LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nat Genet, 2012, 44(11): 1199-1206.

Schleiermacher G, Mosseri V, London WB, Maris JM, Brodeur GM, Attiyeh E, Haber M, Khan J, Nakagawara A, Speleman F, Noguera R, Tonini GP, Fischer M, Ambros I, Monclair T, Matthay KK, Ambros P, Cohn SL, Pearson ADJ
Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project. Brit J Cancer, 2012, 107(8): 1418-1422.

Höpker K, Hagmann H, Khurshid S, Chen S, Hasskamp P, Seeger-Nukpezah T, Schilberg K, Heukamp L, Lamkemeyer T, Sos M, Thomas R, Lowery D, Fischer M, Roels F, Liebau MC, Resch U, Kisner T, Röther F, Bartram MP, Müller RU, Fabretti F, Kurschat P, Schumacher B, Medema R, Yaffe MB, Schermer B, Reinhardt HC, Benzing T
AATF/Che1 acts as a phosphorylation-dependent molecular modulator to repress p53-driven apoptosis. EMBO J, 2012, 31(20): 3961-3975.

Stigliani S, Coco S, Moretti S, Oberthuer A, Fischer M, Theissen J, Gallo F, Garaventa A, Berthold F, Bonassi S, Tonini GP, Scaruffi P.
Identification of novel integrated genomic and RNA signatures associated with progression of metastatic high-risk neuroblastoma. Neoplasia, 2012, 14(9): 823-832.

Asgharzadeh S, Salo JA, Ji L, Oberthuer A, Fischer M, Berthold F, Hadjidaniel M, Liu CWY, Metelitsa LS, Pique-Regi R, Wakamatsu P, Villablanca JG, Kreissman SG, Matthay KK, Shimada H, London WB, Sposto R, Seeger RC
Clinical Significance of Tumor-Associated Inflammatory Cells in Metastatic Neuroblastoma. J Clin Oncol, 2012, 30(28): 3525-3532.

Peifer M, Fernández-Cuesta L, Sos ML, George J, Kasper LH, Seidel D, Plenker D, Leenders F, Sun R, Zander T, Menon R, Koker M, Dahmen I, Müller C, Di Cerbo V, Schildhaus HU, Altmüller J, Baessmann I, Becker C, De Wilde B, Vandesompele J, Böhm D, Ansén S, Gabler F, Wilkening I, Heynck S, Heuckmann JM, Lu X, Cibulskis K, Banerji S, Getz G, Park KS, Rauh D, Grütter C, Fischer M, Pasqualucci L, Wright G, Wainer Z,  Russell P, Petersen I, Chen Y, Stoelben E, Ludwig C, Schnabel P, Hoffmann H, Muley T, Brockmann M, Engel-Riedel W, Muscarella LA, Fazio VM, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman DAM, Snijders PJF, Cappuzzo F, Ligorio C, Damiani S, Field J, Solberg S, Brustugun OT, Lund-Iversen M, Sänger J, Clement JH, Soltermann A, Moch H, Weder W, Solomon B, Soria JC, Validire P, Besse B, Brambilla E, Brambilla C, Lantuejoul S, Lorimier P, Schneider PM, Hallek M, Pao W, Meyerson M, Sage J, Shendure J, Schneider R, Büttner R, Wolf J, Nürnberg P, Perner S, Heukamp LC, Brindle PK, Haas S, Thomas RK
Small cell lung cancer: identification of relevant mutated genes in a highly mutated genome by integrative genome analyses. Nat Genet, 2012, 44(10): 1104-1110.

Frommolt P, Abdallah AT, Altmüller J, Motameny S, Becker C, Stemshorn K, Fischer M, Freilinger T, Nürnberg P
Assessing the enrichment performance in targeted resequencing experiments. Hum Mutat, 2012, 33(4): 635-641.

Garcia I, Mayol G, Rios J, Domenech G, Cheung NK, Oberthuer A, Fischer M, Maris JM, Brodeur GM, Hero B, Rodriguez E, Sunol M, Galvan P, de Torres C, Mora J, Lavarino C.
A three-gene expression signature model for risk stratification of patients with neuroblastoma. Clin Cancer Res, 2012, 18(7): 2012-2023.

Coco S, Theissen J, Scaruffi P, Stigliani S, Moretti S, Oberthuer A, Valdora F, Fischer M, Gallo F, Hero B, Bonassi S, Berthold F, Tonini GP
Age-dependent accumulation of genomic aberrations and deregulation of cell cycle and telomerase genes in metastatic neuroblastoma. Int J Cancer, 2012, 131(7): 1591-1600.

Schulte JH, Bachmann H, Brockmeyer B, DePreter K, Oberthuer A, Ackermann S, Kahlert Y, Pajtler K, Theissen J, Westermann F, Vandesompele J, Speleman F, Berthold F, Eggert A, Brors B, Hero B, Schramm A, Fischer M
High ALK receptor tyrosine kinase expression supersedes ALK mutation as a determining factor of an unfavorable phenotype in primary neuroblastoma. Clin Cancer Res, 2011, 17(15): 5082-5092.

Henrich KO, Bauer T, Schulte J, Ehemann V, Deubzer H, Gogolin S, Muth D, Fischer M, Benner A, König R, Schwab M, Westermann F
CAMTA1, a 1p36 tumor suppressor candidate, inhibits growth and activates differentiation programmes in neuroblastoma cells. Cancer Res, 2011, 71(8): 3142-3151.

Afanasyeva EA, Mestdagh P, Kumps C, Vandesompele J, Ehemann V, Theissen J, Fischer M, Zapatka M, Brors B, Savelyeva L, Sagulenko V, Speleman F, Schwab M, Westermann F
MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival. Cell Death Differ, 2011, 18(6): 974-984.

Ackermann S, Goeser F, Schulte JH, Schramm A, Ehemann V, Eggert A, Hero B, Berthold F, Fischer M
Polo-like kinase 1 is a therapeutic target in high-risk neuroblastoma. Clin Cancer Res, 2011, 17(4): 731-741.

Shi L, Campbell G, Jones WD, Campagne F, Wen Z, Walker SJ, Su Z, Chu TM, Goodsaid FM, Pusztai L, Shaughnessy JD Jr, Oberthuer A, Thomas RS, Paules RS, Fielden M, Barlogie B, Chen W, Du P, Fischer M, Furlanello C, Gallas BD, Ge X, Megherbi DB, Symmans WF, Wang MD, Zhang J, Bitter H, Brors B, Bushel PR, Bylesjo M, Chen M, Cheng J, Cheng J, Chou J, Davison TS, Delorenzi M, Deng Y, Devanarayan V, Dix DJ, Dopazo J, Dorff KC, Elloumi F, Fan J, Fan S, Fan X, Fang H, Gonzaludo N, Hess KR, Hong H, Huan J, Irizarry RA, Judson R, Juraeva D, Lababidi S, Lambert CG, Li L, Li Y, Li Z, Lin SM, Liu G, Lobenhofer EK, Luo J, Luo W, McCall MN, Nikolsky Y, Pennello GA, Perkins RG, Philip R, Popovici V, Price ND, Qian F, Scherer A, Shi T, Shi W, Sung J, Thierry-Mieg D, Thierry-Mieg J, Thodima V, Trygg J, Vishnuvajjala L, Wang SJ, Wu J, Wu Y, Xie Q, Yousef WA, Zhang L, Zhang X, Zhong S, Zhou Y, Zhu S, Arasappan D, Bao W, Lucas AB, Berthold F, Brennan RJ, Buness A, Catalano JG, Chang C, Chen R, Cheng Y, Cui J, Czika W, Demichelis F, Deng X, Dosymbekov D, Eils R, Feng Y, Fostel J, Fulmer-Smentek S, Fuscoe JC, Gatto L, Ge W, Goldstein DR, Guo L, Halbert DN, Han J, Harris SC, Hatzis C, Herman D, Huang J, Jensen RV, Jiang R, Johnson CD, Jurman G, Kahlert Y, Khuder SA, Kohl M, Li J, Li L, Li M, Li QZ, Li S, Li Z, Liu J, Liu Y, Liu Z, Meng L, Madera M, Martinez-Murillo F, Medina I, Meehan J, Miclaus K, Moffitt RA, Montaner D, Mukherjee P, Mulligan GJ, Neville P, Nikolskaya T, Ning B, Page GP, Parker J, Parry RM, Peng X, Peterson RL, Phan JH, Quanz B, Ren Y, Riccadonna S, Roter AH, Samuelson FW, Schumacher MM, Shambaugh JD, Shi Q, Shippy R, Si S, Smalter A, Sotiriou C, Soukup M, Staedtler F, Steiner G, Stokes TH, Sun Q, Tan PY, Tang R, Tezak Z, Thorn B, Tsyganova M, Turpaz Y, Vega SC, Visintainer R, von Frese J, Wang C, Wang E, Wang J, Wang W, Westermann F, Willey JC, Woods M, Wu S, Xiao N, Xu J, Xu L, Yang L, Zeng X, Zhang J, Zhang L, Zhang M, Zhao C, Puri RK, Scherf U, Tong W, Wolfinger RD; MAQC Consortium.
The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models. Nat Biotechnol, 2010, 28(8): 827-838.

Parry RM, Jones W, Stokes TH, Phan JH, Moffitt RA, Fang H, Shi L, Oberthuer A, Fischer M, Tong W, Wang MD
k-Nearest neighbor models for microarray gene expression analysis and clinical outcome prediction. Pharmacogenomics J, 2010, 10: 292-309.

Oberthuer A, Juraeva D, Li L, Kahlert Y, Westermann F, Eils R, Berthold F, Shi L, Wolfinger RD, Fischer M, Brors B
Comparison of performance of one-color and two-color gene-expression analyses in predicting clinical endpoints of neuroblastoma patients. Pharmacogenomics J, 2010, 10: 258-266.

Oberthuer A, Hero B, Berthold F, Juraeva D, Faldum A, Kahlert Y, Asgharzadeh S, Seeger R, Scaruffi P, Tonini GP, Janoueix-Lerosey I, Delattre O, Schleiermacher G, Vandesompele J, Vermeulen J, Speleman F, Noguera R, Piqueras M, Bénard J, Valent A, Avigad S, Yaniv I, Weber A, Christiansen H, Grundy RG, Schardt K, Schwab M, Eils R, Warnat P, Kaderali L, Simon T, DeCarolis B, Theissen J, Westermann F, Brors B, Fischer M
Prognostic impact of gene expression-based classification for neuroblastoma. J Clin Oncol, 2010, 28(21): 3506-3515.

Muth D, Ghazaryan S, Eckerle I, Beckett E, Pöhler C, Batzler J, Beisel C, Gogolin S, Fischer M, Henrich KO, Ehemann V, Gillespie P, Schwab M, Westermann F
Transcriptional repression of SKP2 is impaired in MYCN-amplified neuroblastoma. Cancer Res, 2010, 70(9): 3791-3802.

De Preter K, Vermeulen J, Brors B, Delattre O, Eggert A, Fischer M, Janoueix-Lerosey I, Lavarino C, Maris J, Mora J, Nakagawara A, Oberthür A, Ohira M, Schleiermacher G, Schramm A, Schulte J, Wang Q, Westermann F, Speleman F, Vandesompele J
Accurate outcome prediction in neuroblastoma across independent datasets using a multi-gene signature. Clin Cancer Res, 2010, 16(5): 1532-1541.

Fischer M, Bauer T, Oberthür A, Hero B, Theissen J, Ehrich M, Spitz R, Westermann F, Brors B, König R, Berthold F
Integrated genomic profiling identifies two distinct molecular subtypes with divergent outcome in neuroblastoma with loss of chromosome 11q. Oncogene, 2010, 29(6): 865-875.

Nevo I, Oberthür A, Edri-Botzer L, Sagi-Assif O, Pasmanik-Chor M, Kariv N, Fischer M, Yron I, Witz IP
Gene-expression-based analysis of local and metastatic neuroblastoma variants reveals a set of genes associated with tumor progression in neuroblastoma patients. Int J Cancer, 2010, 126(7):1570-81.

Harel L, Tcherpakov M, Costa B, Zapatka M, Oberthuer A, Hansford LM, Levy Z, Avigad S, Yaniv I, Shi L, Eils R, Fischer M, Brors B, Kaplan DR, Fainzilber M
CCM2 mediates death signalling by the TrkA receptor tyrosine kinase. Neuron, 2009, 63(5): 585-591.

Hoene V, Fischer M, Ivanova A, Wallach T, Berthold F, Dame C
GATA factors in human neuroblastoma: distinctive expression patterns in clinical subtypes. Brit J Cancer, 2009, 101(8): 1481-1489.

Vermeulen J, De Preter K, Naranjo A, Vercruysse L, Van Roy N, Hellemans J, Swerts K, Bravo S, Scaruffi P, Tonini GP, De Bernardi B, Noguera R, Piqueras M, Canete A, Castel V, Janoueix-Lerosey I, Delattre O, Schleiermacher G, Michon J, Combaret V, Fischer M, Oberthür A, Ambros P, Beiske K, Benard J, Marques B, Rubie H, Kohler J, Pötschger U, Ladenstein R, Hogarty MD, McGrady P, London WB, Laureys G, Speleman F, Vandesompele J
Predicting outcomes for children with neuroblastoma using a multigene-expression signature, a retrospective SIOPEN/COG/GPOH study. Lancet Oncol, 2009, 10(7): 663-671.

Eckerle I, Muth D, Batzler J, Henrich KO, Lutz W, Fischer M, Witt O, Schwab M, Westermann F
Regulation of BIRC5 and its isoform BIRC5-2B in neuroblastoma. Cancer Lett, 2009, 285(1): 99-107.

Voth H, Oberthür A, Simon T, Kahlert Y, Berthold F, Fischer M
Co-regulated expression of HAND2 and DEIN by a bidirectional promoter with asymmetrical activity in neuroblastoma. BMC Mol Biol, 2009, 10:28.

Oehme I, Deubzer HE, Wegener D, Pickert D, Linke JP, Hero B, Kopp-Schneider A, Westermann F, Ulrich S, Fischer M, Witt O
Histone deacetylase 8 in neuroblastoma tumorigenesis. Clin Cancer Res, 2009, 15(1): 91-99.

Westermann F, Muth D, Benner A, Bauer T, Henrich KO, Oberthür A, Brors B, Beissbarth T, Vandesompele J, Pattyn F, Hero B, König R, Fischer M, Schwab M
Distinct transcriptional MYCN/c-MYC activities are associated with spontaneous regression or malignant progression in neuroblasotmas. Genome Biol, 2008, 9(10): R150.

Oberthür A, Kaderali L, Kahlert Y, Hero B, Westermann F, Berthold F, Brors B, Eils R, Fischer M
Sub-classification and individual survival time prediction from gene-expression data of neuroblastoma patients using CASPAR. Clin Cancer Res, 2008, 14(20): 6590-6601.

Bénard J, Raguénez G, Kauffmann A, Valent A, Ripoche H, Joulin V, Job B, Danglot G, Cantais S, Robert T, Terrier-Lacombe MJ, Chassevent A, Koscielny S, Fischer M, Berthold F, Lipinski M, Tursz T, Dessen P, Lazar V, Valteau-Couanet D
MYCN-non-amplified metastatic neuroblastoma with good prognosis and spontaneous regression: A molecular portrait of stage 4S. Mol Oncol, 2008, 2(3): 261-271.

Pawlowski M, Kouklinos A, Jopp-Petzina G, Herkenrath P, Fischer M, Kribs A, Roth B, Roth J, Tenbrock K
G/A polymorphism at -258 of the hepatic glucokinase promoter is not associated with decreased birth weight in preterm neonates. Neonatology, 2008, 94(2): 71-74.

Nowacki S, Skowron M, Oberthür A, Fagin A, Voth H, Brors B, Westermann F, Eggert A, Hero B, Berthold F, Fischer M
Expression of the tumour suppressor gene CADM1 is associated with favourable outcome and inhibits cell survival in neuroblastoma. Oncogene, 2008, 27(23): 3329-3338.

Voth H, Oberthür A, Simon T, Kahlert Y, Berthold F, Fischer M
Identification of DEIN, a novel gene with high expression levels in stage 4S neuroblastoma. Mol Cancer Res, 2007, 5(12): 1276-1284.

Westermann F, Henrich KO, Wei JS, Lutz W, Fischer M, König R, Wiedemeyer R, Ehemann V, Brors B, Ernestus K, Leuschner I, Benner A, Khan J, Schwab M
High Skp2 expression characterizes high-risk neuroblastomas independent of MYCN status. Clin Cancer Res, 2007, 13(16): 4695-4703.

Warnat P, Oberthür A, Fischer M, Westermann F, Eils R, Brors B
Cross-study analysis of gene expression data for advanced stage neuroblastoma tumors without MYCN amplification suggests two biological entities associated with contrasting clinical outcome. BMC Cancer, 2007, 7: 89.

Oberthür A, Warnat P, Kahlert Y, Westermann F, Spitz R, Brors B, Eils R, Schwab M, Berthold F, Fischer M
Classification of neuroblastoma patients by published gene-expression markers reveals a low sensitivity for unfavorable courses of MYCN non-amplified disease. Cancer Lett, 2007, 250(2): 250-267.

Oberthür A, Berthold F, Warnat P, Hero B, Kahlert Y, Spitz R, Ernestus K, König R, Haas S, Eils R, Schwab M, Brors B, Westermann F, Fischer M
Customized oligonucleotide microarray gene-expression based classification of neuroblastoma patients outperforms current clinical risk stratification. J Clin Oncol, 2006, 24: 5070-5078.

Spitz R, Oberthür A, Zapatka M, Brors B, Hero B, Ernestus K, Östreich J, Fischer M, Simon T, Berthold F
Oligonucleotide array-based comparative genomic hybridization (aCGH) of 90 neuroblastoma reveals aberration patterns closely associated with relapse pattern and outcome. Gene Chromosome Canc, 2006, 45(12): 1130-1142.

Fischer M, Oberthür A, Brors B, Kahlert Y, Skowron M, Voth H, Warnat P, Ernestus K, Hero B, Berthold F
Differential expression of neuronal genes define subtypes of disseminated neuroblastoma with favorable and unfavorable outcome. Clin Cancer Res, 2006, 12(17): 5118-5128.

Henrich KO, Fischer M, Mertens D, Benner A, Wiedemeyer R, Brors B, Oberthür A, Berthold F, Wei J, Khan J, Schwab M, Westermann F
Reduced expression of CAMTA1 correlates with adverse outcome in neuroblastoma patients. Clin Cancer Res, 2006, 12(1): 131-138.

Oberthür A, Skowron M, Spitz R, Kahlert Y, Westermann F, Mehler K, Berthold F, Fischer M
Characterization of a complex genomic alteration on chromosome 2p that leads to four alternatively spliced fusion transcripts in the neuroblastoma cell lines IMR-5, IMR-5/75 and IMR-32. Gene, 2005, 363: 41-50.

Boensch M, Oberthür A, Fischer M, Skowron M, Oestreich J, Berthold F, Spitz R
Quantitative real-time PCR for quick simultaneous determination of therapy-stratifying markers MYCN amplification, deletion of 1p and 11q. Diagn Mol Pathol, 2005, 14(3): 177-182.

Fischer M, Skowron M, Berhold F
Reliable transcript quantification by real-time reverse transcriptase-polymerase chain reaction in primary neuroblastoma using normalization to averaged expression levels of the control genes HPRT1 and SDHA. J Mol Diagn, 2005, 7(1): 89-96.

Oberthür A, Hero B, Spitz R, Berthold F, Fischer M
The tumor-associated antigen PRAME is universally expressed in high stage neuroblastoma and associated with poor outcome. Clin Cancer Res, 2004, 10(13): 4307-4313.

Fischer M, Berthold F
Characterization of the gene expression profile of neuroblastoma cell line IMR-5 using Serial Analysis of Gene Expression. Cancer Lett, 2003, 190: 79-87.

Fischer M, Küppers R
Human IgA- and IgM-secreting intestinal plasma cells carry heavily mutated VH region genes. Eur J Immunol, 1998, 28(9): 2971-2977.

Fischer M, Klein U, Küppers R
Molecular single-cell analysis reveals that CD5-positive peripheral blood B cells in healthy humans are characterized by rearranged V genes lacking somatic mutation. J Clin Invest, 1997, 100(7): 1667-1676.


II Übersichtsarbeiten

Simon T, Hero B, Schulte JH, Deubzer H, Hundsdoerfer P, von Schweinitz D, Fuchs J, Schmidt M, Prasad V, Krug B, Timmermann B, Leuschner I, Fischer M, Langer T, Astrahantseff K, Berthold B, Lode H, Eggert A
2017 GPOH Guidelines for Diagnosis and Treatment of Patients with Neuroblastic Tumors. . Klin Padiatr, in press.

Hertwig F, Peifer M, Fischer M
Telomere maintenance is pivotal for high-risk neuroblastoma. Cell Cycle, 2016, 15(3): 311-312.

Schulte JH, Schulte S, Heukamp LC, Astrahantseff K, Stephan H, Fischer M, Schramm A, Eggert A
Targeted therapy for neuroblastoma: ALK inhibitors. Klin Padiatr, 2013, 225(6): 303-308.

Fischer M, Berthold F
The role of complex genomic alterations in neuroblastoma risk estimation. Genome Med, 2010, 2: 31.

Oberthuer A, Theissen J, Westermann F, Hero B, Fischer M
Molecular characterization and classification of neuroblastoma. Future Oncol, 2009, 5(5): 625-639.

Fischer M, Spitz R, Oberthür A, Westermann F, Berthold F
Risk estimation of neuroblastoma patients using molecular markers. Klin Padiatr, 2008, 220: 137-146.

Fischer M, Oberthür A, von Schweinitz D, Simon T
Das Neuroblastom. Onkologe, 2005, 11: 1054-1064.

Klein U, Goossens T, Fischer M, Kanzler H, Braeuninger A, Rajewsky K, Küppers R
Somatic hypermutation in normal and transformed B cells. Immunol Rev, 1998, 162: 261-280.

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